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distal convoluted tubule

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https://www.readbyqxmd.com/read/28534087/interspecies-differences-in-pth-mediated-pka-phosphorylation-of-the-epithelial-calcium-channel-trpv5
#1
Mark K van Goor, Sjoerd Verkaart, Teunis J van Dam, Martijn A Huynen, Jenny van der Wijst
The epithelial calcium (Ca(2+)) channel TRPV5 (transient receptor potential vanilloid 5) is expressed in the distal convoluted tubule of the kidney and facilitates active Ca(2+) reabsorption. This process is instrumental for the maintenance of Ca(2+) homeostasis. Therefore, all aspects of TRPV5 function are tightly regulated by the calciotropic parathyroid hormone (PTH). Rabbit (rb)TRPV5 channel activity was shown to be stimulated upon PTH-mediated protein kinase A (PKA) phosphorylation. Since there is incomplete conservation of the PKA consensus motif (RR/QxT) across species, the aim of this study was to extend these findings to humans and characterize the expression and function of human (h)TRPV5...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28499081/negative-correlation-between-serum-uric-acid-and-kidney-urat1-mrna-expression-caused-by-resveratrol-in-rats
#2
Cheng-Tse Lee, Li-Ching Chang, Ching-Wen Liu, Pei-Fung Wu
SCOPE: This study established a hyperuricemic rat model to elucidate the effect of resveratrol on the transport of UA in the kidney. METHODS AND RESULTS: Hyperuricemia was induced in rats through daily oral gavage of a potassium oxonate and UA mixture over 3 weeks. Our results revealed that resveratrol significantly reduced the serum UA levels but not creatinine, c-creative protein, alanine aminotransferase, or aspartate aminotransferase levels in these rats. Furthermore, renal URAT1 and OAT1 mRNA expression were significantly higher in the rats treated with allopurinol than in those with no treatment...
May 12, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28471235/mechanism-of-grape-seeds-extract-protection-against-paracetamol-renal-cortical-damage-in-male-albino-rats
#3
S M N Abdel-Hafez, R A Rifaai, W Y Abd Elzaher
OBJECTIVE: The aim of the study was to assess the possible protective role of grape seeds extract (GSE) in ameliorating the toxic effects of paracetamol overdose on the rat renal cortical tissue. BACKGROUND: Paracetamol is one of the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Unfortunately, it was reported as the most common cause of toxic ingestion in the world. Grape seeds extract (GSE) is known to have a strong antioxidant and anti-inflammatory properties...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#4
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28414128/impaired-degradation-of-medullary-wnk4-in-the-kidneys-of-klhl2-knockout-mice
#5
Yuri Kasagi, Daiei Takahashi, Tomomi Aida, Hidenori Nishida, Naohiro Nomura, Moko Zeniya, Takayasu Mori, Emi Sasaki, Fumiaki Ando, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and Cullin3 (CUL3) genes were identified as being responsible for hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC cascade in the kidney's distal convoluted tubules (DCT)...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28408636/aldosterone-regulates-a-5-variant-sgk1-transcript-via-a-shared-hormone-response-element-in-the-sgk1-5-regulatory-region
#6
Nandita S Raikwar, Christie P Thomas
We previously identified a 5' variant alternate transcript of Sgk1 (Sgk1_v3) encoding an NH2-terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is expressed in the distal convoluted tubule, connecting tubule and collecting duct and can stimulate epithelial Na(+) transport (Am J Physiol Renal Physiol 303: F1527-F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers that increase endogenous aldosterone secretion including dietary Na(+) deprivation and K(+) loading increases distal nephron Sgk1_v3 expression in vivo...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28375568/fludrocortisone-therapy-for-persistent-hyperkalaemia
#7
S J H Dobbin, J R Petrie, M E J Lean, G A McKay
Hyperkalaemia is often seen in individuals with renal impairment and may be exacerbated, particularly in diabetic nephropathy, by hyporeninaemic aldosterone deficiency (type 4 renal tubular acidosis) which may, in turn, be caused or complicated by chronic interstitial nephritis or drug therapy (Table 1). Fludrocortisone is a synthetic corticosteroid with mineralocorticoid activity that increases sodium resorption and promotes potassium excretion in the distal convoluted renal tubule. It therefore seems a logical option to reverse hyperkalaemia in type 4 renal tubular acidosis; however, we can find no published guideline recommending this use [1,2]...
April 4, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28373577/parathyroid-hormone-controls-paracellular-ca-2-transport-in-the-thick-ascending-limb-by-regulating-the-tight-junction-protein-claudin14
#8
Tadatoshi Sato, Marie Courbebaisse, Noriko Ide, Yi Fan, Jun-Ichi Hanai, Jovana Kaludjerovic, Michael J Densmore, Quan Yuan, Hakan R Toka, Martin R Pollak, Jianghui Hou, Beate Lanske
Renal Ca(2+) reabsorption is essential for maintaining systemic Ca(2+) homeostasis and is tightly regulated through the parathyroid hormone (PTH)/PTHrP receptor (PTH1R) signaling pathway. We investigated the role of PTH1R in the kidney by generating a mouse model with targeted deletion of PTH1R in the thick ascending limb of Henle (TAL) and in distal convoluted tubules (DCTs): Ksp-cre;Pth1r(fl/fl) Mutant mice exhibited hypercalciuria and had lower serum calcium and markedly increased serum PTH levels. Unexpectedly, proteins involved in transcellular Ca(2+) reabsorption in DCTs were not decreased...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28366875/dual-role-of-muc1-mucin-in-kidney-ischemia-reperfusion-injury-nephroprotector-in-early-phase-but-pro-fibrotic-in-late-phase
#9
Jean-Baptiste Gibier, Brigitte Hémon, Mélanie Fanchon, Kelly Gaudelot, Nicolas Pottier, Bélinda Ringot, Isabelle Van Seuningen, François Glowacki, Christelle Cauffiez, David Blum, Marie-Christine Copin, Michaël Perrais, Viviane Gnemmi
Acute kidney injury (AKI) is characterized by acute tubular necrosis (ATN) which involves mainly proximal tubules. Past AKI is associated with higher risk of chronic kidney disease (CKD). The MUC1 mucin is a large glycoprotein responsible for epithelial protection and locates to convoluted distal tubules and collecting ducts. Since MUC1 activates the epithelial-mesenchymal transition (EMT) in carcinoma cells, we hypothesized that MUC1 could be involved in epithelial tubular cell plasticity, a process that not only accompanies epithelial repair, but also participates into kidney fibrosis, histological substratum of CKD...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28365586/enac-and-romk-activity-are-inhibited-in-the-dct2-cnt-of-tgwnk4-phaii-mice
#10
Chengbiao Zhang, Lijun Wang, Xiao-Tong Su, Junhui Zhang, Dao-Hong Lin, Wen-Hui Wang
Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4(PHAII)) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na(+) delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na(+) channel (ENaC) and renal outer medullary K(+) channel (ROMK or Kir4.1) are expressed in the late DCT and play an important role in mediating K(+) secretion, the aim of the present study is to test whether ROMK and ENaC activity in the DCT/CNT are also compromised in the mice expressing PHAII mutant Wnk4...
April 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28356287/pgf2%C3%AE-regulates-the-basolateral-k-channels-in-the-distal-convoluted-tubule-dct
#11
Lijun Wang, Chengbiao Zhang, Xiao-Tong Su, Dao-Hong Lin, Peng Wu, Michal Laniado Schwartzman, Wen-Hui Wang
We aim to examine the role of PGF2α receptor (FP), a highly expressed prostaglandin receptor in the DCT, in regulating basolateral 40 pS K channel. The single channel studies demonstrated that PGF2α had a biphasic effect on the 40 pS K channel in the DCT: PGF2α stimulated at low concentrations (less than 500 nM) while at high concentrations (above 1µM) it inhibited the 40 pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF2α (a metabolite of PGF2α) nor PGE2 was able to mimic the effect of PGF2α on the 40 pS K channel in the DCT...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28341694/mineralocorticoid-receptor-and-nacl-transport-mechanisms-in-the-renal-distal-nephron
#12
Shigeru Shibata
A key role of aldosterone and mineralocorticoid receptor is to regulate fluid volume and K+ homeostasis in the body by acting on the renal distal nephron. Global responses of the kidney to elevated aldosterone levels are determined by the coordinate action of different constituent tubule cells, including principal cells, intercalated cells, and distal convoluted tubule cells. Recent studies on genetic mutations causing aldosterone overproduction have identified molecules involved in aldosterone biosynthesis in the adrenal gland, and there is also increasing evidence for mechanisms and signaling pathways regulating the balance between renal NaCl reabsorption and K+ secretion, the two major effects of aldosterone...
March 24, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#13
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28292888/antibody-mediated-inhibition-of-egfr-reduces-phosphate-excretion-and-induces-hyperphosphatemia-and-mild-hypomagnesemia-in-mice
#14
Bernardo Ortega, Jason M Dey, Allison R Gardella, Jacob Proano, Deanna Vaneerde
Monoclonal antibody therapies targeting the EGF receptor (EGFR) frequently result in hypomagnesemia in human patients. In contrast, EGFR tyrosine kinase inhibitors do not affect Mg(2+) balance in patients and only have a mild effect on Mg(2+) homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (Pi) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at Pi excretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg(2+) and/or Pi in the kidney remains controversial...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28289184/renal-tubular-ubiquitin-protein-ligase-nedd4-2-is-required-for-renal-adaptation-during-long-term-potassium-depletion
#15
Lama Al-Qusairi, Denis Basquin, Ankita Roy, Renuga Devi Rajaram, Marc P Maillard, Arohan R Subramanya, Olivier Staub
Adaptation of the organism to potassium (K(+)) deficiency requires precise coordination among organs involved in K(+) homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K(+) retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na(+)/Cl(-) cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K(+) restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L(Pax8/LC1) ) mice exhibited severe hypokalemia and urinary K(+) wasting...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28274929/hydrochlorothiazide-treatment-increases-the-abundance-of-the-nacl-cotransporter-in-urinary-extracellular-vesicles-of-essential-hypertensive-patients
#16
Ganesh Pathare, Omar A Z Tutakhel, Mark C V D Wel, Luke M Shelton, Jaap Deinum, Jacques W Lenders, Joost G J Hoenderop, René J M Bindels
The thiazide-sensitive NaCl cotransporter (NCC), located apically in distal convoluted tubule epithelia, regulates the fine-tuning of renal sodium excretion. Three isoforms of NCC are generated through alternative splicing of the transcript, of which the third isoform has been the most extensively investigated in pathophysiological conditions. The aim of this study was to investigate the effect of different anti-hypertensive treatments on the abundance and phosphorylation of all three NCC isoforms in urinary extracellular vesicles (uEVs) of essential hypertensive patients...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28274923/effect-of-diuretics-on-renal-tubular-transport-of-calcium-and-magnesium
#17
R Todd Alexander, Henrik Dimke
Calcium (Ca2+) and Magnesium (Mg2+) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca2+ and Mg2+ reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation permeable pores and channels, but also for generating the necessary driving forces for Ca2+ and Mg2+ transport. Alterations in these molecular constituents lead to profound effects on tubular Ca2+ and Mg2+ handling...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28254523/transcriptomic-analysis-and-plasma-metabolomics-in-aldh16a1-null-mice-reveals-a-potential-role-of-aldh16a1-in-renal-function
#18
Georgia Charkoftaki, Ying Chen, Ming Han, Monica Sandoval, Xiaoqing Yu, Hongyu Zhao, David J Orlicky, David C Thompson, Vasilis Vasiliou
ALDH16A1 is a novel member of the ALDH superfamily that is enzymatically-inactive and highly expressed in the kidney. Recent studies identified an association between a rare missense single nucleotide variant (SNV) in the ALDH16A1 gene and elevated serum uric acid levels and gout. The present study explores the mechanisms by which ALDH16A1 influences uric acid homeostasis in the kidney. We generated and validated a mouse line with global disruption of the Aldh16a1 gene through gene targeting and performed RNA-seq analyses in the kidney of wild-type (WT) and Aldh16a1 knockout (KO) mice, along with plasma metabolomics...
February 28, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28125972/gitelman-syndrome-in-a-south-african-family-presenting-with-hypokalaemia-and-unusual-food-cravings
#19
Pieter Du Toit van der Merwe, Megan A Rensburg, William L Haylett, Soraya Bardien, M Razeen Davids
BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterised by renal salt wasting with hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is caused by mutations in SLC12A3 encoding the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule. We report a South African family with five affected individuals presenting with hypokalaemia and unusual food cravings. METHODS: The affected individuals and two unaffected first degree relatives were enrolled into the study...
January 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28120456/endothelin-1-mediates-natriuresis-but-not-polyuria-during-vitamin-d-induced-acute-hypercalcaemia
#20
Natsuko Tokonami, Lydie Cheval, Isabelle Monnay, Guillaume Meurice, Johannes Loffing, Eric Feraille, Pascal Houillier
KEY POINTS: Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism. A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)-1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia-induced effects. In the present study, we demonstrate that, during vitamin D-induced hypercalcaemia, the activation of ET system by increased ET-1 is responsible for natriuresis but not for polyuria...
April 15, 2017: Journal of Physiology
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